Expression and significance of PCS, PC7, VEGF-C, VEGF-D and VEGFR-3 mRNA in non-small cell lung cancer / 中国癌症杂志

ABSTRACT

Background and purpose: Infiltration and metastasis are characteristic of the biological behavior of cancer. Blood circulation and lymphatic spread are two important ways for neoplasm metastasis. The lymphatic vessel is one of the earliest routes for solid neoplasm metastasis. However, compared to tumor blood vessels, there were only a few studies on the research for lymphatic vessel spread. In recent years, with the identification of vascular endothelial growth factor-C (VEGF-C), VEGF-D and lymphatic endothelial markers including lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3), glomerular podocyte membrance mucoprotein (podoplanin) and the homeobox transcription factor (Prox-1), lymphangiogenesis has become one of the important areas in the study of tumor metastasis. This paper was to study the expression of proprotein convertase (PC)5, PC7, VEGF-C, VEGF-D and their receptor VEGFR-3 in patients with non-small cell lung cancer (NSCLC) and their clinico-pathoiogical value. Methods: Twenty specimens of the NSCLC, peritumoral tissues as experimental group and nine pulmonary benign diseases as control group were studied. The expression of PC5, PC7, VEGF-C, VEGF-D and VEGFR-3 mRNA in specimens of those tissues were studied by real-time quantitative reverse transcriptase polymerase chain reaction (real-time quantitative RT-PCR). Results: ①The expressions of PC5, PC7, VEGF-C, VEGF-D, VEGFR-3 mRNA in specimens of NSCLC were significantly higher than those of the peritumoral and pulmonary benign diseases tissues (P<O.05).② The expressions of PC5, PC7, VEGF-C, VEGF-D and VEGFR-3 mRNA in NSCLC were not correlated with age, gender, site and dimension of lesion, types of histological and degree of differentiation, but correlated significantly with lymph node metastasis (P=0.000, P=0.000,P=0.012,P=O.000, P=0.004) and pTNM stage (P=0.011, P=0.012, P=0.O13, P=0.011, P=0.028).③Significant correlationsbetween PC5 and VEGF-C (r=0.461, P=0.041), PC5 and VEGF-D (r=0.793, P=0.000), PC5 and VEGFR-3 (r=0.498, P=0.026), PC7 and VEGF-C (r=0.450, P=0.047), PC7 and VEGF-D (r=0.699, P=0.001), PC7 and VEGFR-3 (r=0.616, P=0.004), VEGF-C and VEGF-D (r=0.532, P=0.016), VEGF-C and VEGFR-3 (r=0.607, P=0.001), VEGF-D and VEGFR-3 (r=0.451, P=0.048) mRNA were observed in NSCLC. Conclusion: Non-small cell lung cancer cells may secrete lymphangiogenetic growth factors like VEGF-C, VEGF-D and their receptor VEGFR-3 and may associate with lymphatic metastasis of NSCLC through their downstream pathways. The expression of VEGF-C, VEGF-D, VEGFR-3, PC5 and PC7 may serve as important markers for evaluation of lymphatic metastasis and prognosis in patients with NSCLC.